DE3326472A1 - Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus - Google Patents
Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitusInfo
- Publication number
 - DE3326472A1 DE3326472A1 DE19833326472 DE3326472A DE3326472A1 DE 3326472 A1 DE3326472 A1 DE 3326472A1 DE 19833326472 DE19833326472 DE 19833326472 DE 3326472 A DE3326472 A DE 3326472A DE 3326472 A1 DE3326472 A1 DE 3326472A1
 - Authority
 - DE
 - Germany
 - Prior art keywords
 - insulin
 - formula
 - arg
 - insulin derivative
 - stands
 - Prior art date
 - Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
 - Withdrawn
 
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims description 134
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 - 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
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 - 239000005556 hormone Substances 0.000 description 1
 - 150000002431 hydrogen Chemical class 0.000 description 1
 - QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
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 - 239000002207 metabolite Substances 0.000 description 1
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 - 206010033675 panniculitis Diseases 0.000 description 1
 - FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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 - COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
 - COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
 - 230000004962 physiological condition Effects 0.000 description 1
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 - 102000005962 receptors Human genes 0.000 description 1
 - 108020003175 receptors Proteins 0.000 description 1
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 - 238000007127 saponification reaction Methods 0.000 description 1
 - 239000001509 sodium citrate Substances 0.000 description 1
 - NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
 - 235000011083 sodium citrates Nutrition 0.000 description 1
 - 239000001488 sodium phosphate Substances 0.000 description 1
 - 229910000162 sodium phosphate Inorganic materials 0.000 description 1
 - 235000011008 sodium phosphates Nutrition 0.000 description 1
 - PANBYUAFMMOFOV-UHFFFAOYSA-N sodium;sulfuric acid Chemical compound [Na].OS(O)(=O)=O PANBYUAFMMOFOV-UHFFFAOYSA-N 0.000 description 1
 - 238000003756 stirring Methods 0.000 description 1
 - 210000004304 subcutaneous tissue Anatomy 0.000 description 1
 - WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
 - 230000009897 systematic effect Effects 0.000 description 1
 - 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
 - 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
 - 238000012360 testing method Methods 0.000 description 1
 - 229940124597 therapeutic agent Drugs 0.000 description 1
 - RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
 - 150000003751 zinc Chemical class 0.000 description 1
 - 239000011592 zinc chloride Substances 0.000 description 1
 - 235000005074 zinc chloride Nutrition 0.000 description 1
 
Classifications
- 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07K—PEPTIDES
 - C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
 - C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
 - C07K14/575—Hormones
 - C07K14/62—Insulins
 - C07K14/622—Insulins at least 1 amino acid in D-form
 
 - 
        
- A—HUMAN NECESSITIES
 - A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
 - A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
 - A61P3/00—Drugs for disorders of the metabolism
 - A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
 
 - 
        
- A—HUMAN NECESSITIES
 - A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
 - A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
 - A61P3/00—Drugs for disorders of the metabolism
 - A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
 - A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
 
 - 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07K—PEPTIDES
 - C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
 - C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
 - C07K14/575—Hormones
 - C07K14/62—Insulins
 
 - 
        
- A—HUMAN NECESSITIES
 - A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
 - A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
 - A61K38/00—Medicinal preparations containing peptides
 
 - 
        
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
 - Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
 - Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
 - Y10S930/00—Peptide or protein sequence
 - Y10S930/01—Peptide or protein sequence
 - Y10S930/26—Containing cys-cys disulfide bridge between nonadjacent cysteine residues
 
 
Landscapes
- Health & Medical Sciences (AREA)
 - Chemical & Material Sciences (AREA)
 - Life Sciences & Earth Sciences (AREA)
 - Organic Chemistry (AREA)
 - Diabetes (AREA)
 - Endocrinology (AREA)
 - General Health & Medical Sciences (AREA)
 - Medicinal Chemistry (AREA)
 - Molecular Biology (AREA)
 - Biochemistry (AREA)
 - Gastroenterology & Hepatology (AREA)
 - Biophysics (AREA)
 - Zoology (AREA)
 - Genetics & Genomics (AREA)
 - Toxicology (AREA)
 - Proteomics, Peptides & Aminoacids (AREA)
 - Obesity (AREA)
 - Animal Behavior & Ethology (AREA)
 - Public Health (AREA)
 - Veterinary Medicine (AREA)
 - Pharmacology & Pharmacy (AREA)
 - Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
 - General Chemical & Material Sciences (AREA)
 - Chemical Kinetics & Catalysis (AREA)
 - Hematology (AREA)
 - Bioinformatics & Cheminformatics (AREA)
 - Engineering & Computer Science (AREA)
 - Emergency Medicine (AREA)
 - Peptides Or Proteins (AREA)
 - Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
 
Priority Applications (25)
| Application Number | Priority Date | Filing Date | Title | 
|---|---|---|---|
| DE19833326472 DE3326472A1 (de) | 1983-07-22 | 1983-07-22 | Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus | 
| HU842766A HUT37805A (en) | 1983-07-22 | 1984-07-16 | Process for production of new insuline derivatives and medical preparatives containing them | 
| AR84297267A AR241864A1 (es) | 1983-07-22 | 1984-07-17 | Procedimiento para la preparacion de un medicamento basado en nuevos derivados de insulina. | 
| EP84108442A EP0132770B1 (de) | 1983-07-22 | 1984-07-18 | Neue Insulin-Derivate, Verfahren zu deren Herstellung und deren Verwendung sowie pharmazeutische Mittel zur Behandlung des Diabetes mellitus | 
| AT84108442T ATE29729T1 (de) | 1983-07-22 | 1984-07-18 | Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus. | 
| DE8484108442T DE3466227D1 (en) | 1983-07-22 | 1984-07-18 | Insulin derivatives, processes for their preparation, their use and pharmaceutical compositions for the treatment of diabetes mellitus | 
| GR75343A GR81551B (pm) | 1983-07-22 | 1984-07-18 | |
| FI842914A FI79854C (fi) | 1983-07-22 | 1984-07-19 | Foerfarande foer framstaellning av ett laekemedelspreparat som innehaoller ett insulinderivat. | 
| PT78940A PT78940A (de) | 1983-07-22 | 1984-07-19 | Neue insulin-derivate verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus | 
| NO842977A NO167810C (no) | 1983-07-22 | 1984-07-20 | Analogifremgangsmaate til fremstilling av insulinderivater. | 
| IL72469A IL72469A (en) | 1983-07-22 | 1984-07-20 | Insulin derivatives,process for their preparation and pharmaceutical compositions for the treatment of diabetes mellitus | 
| NZ208959A NZ208959A (en) | 1983-07-22 | 1984-07-20 | Insulin derivatives and pharmaceutical compositions | 
| CA000459386A CA1246548A (en) | 1983-07-22 | 1984-07-20 | Insulin derivatives, processes for their preparation and their use, and pharmaceutical agents for the treatment of diabetes mellitus | 
| DK358284A DK172211B1 (da) | 1983-07-22 | 1984-07-20 | Basisk modificeret insulin-derivat | 
| IE1889/84A IE57709B1 (en) | 1983-07-22 | 1984-07-20 | Novel insulin derivatives,processes for their preparation and their use,and pharmaceutical agents for the treatment of diabetes mellitus | 
| KR1019840004284A KR920005659B1 (ko) | 1983-07-22 | 1984-07-20 | 인슐린 유도체의 제조방법 | 
| AU30922/84A AU569097B2 (en) | 1983-07-22 | 1984-07-20 | Insulin derivatives | 
| ZA845620A ZA845620B (en) | 1983-07-22 | 1984-07-20 | Novel insulin derivatives,processes for their preparation and their use,and pharmaceutical agents for the treatment of diabetes mellitus | 
| JP59149784A JPS6042397A (ja) | 1983-07-22 | 1984-07-20 | 新規なインシユリン誘導体およびそれらの製造法 | 
| PH31009A PH23014A (en) | 1983-07-22 | 1984-07-20 | Novel insulin derivatives,their use and pharmaceutical agents for the treatment of diabetes mellitus | 
| ES534487A ES534487A0 (es) | 1983-07-22 | 1984-07-20 | Procedimiento para la preparacion de un derivado de insulina | 
| ES535706A ES8505646A1 (es) | 1983-07-22 | 1984-09-06 | Procedimiento para la preparacion de un derivado de insulina | 
| US06/873,456 US4701440A (en) | 1983-07-22 | 1986-06-06 | Insulin derivatives, processes for their preparation and their use, and pharmaceutical agents for the treatment of diabetes mellitus | 
| JP1040427A JPH01294634A (ja) | 1983-07-22 | 1989-02-22 | 糖尿病治療用医薬 | 
| DK001790A DK172209B1 (da) | 1983-07-22 | 1990-01-04 | Lægemidler indeholdende basisk modificerede insulinderivater | 
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title | 
|---|---|---|---|
| DE19833326472 DE3326472A1 (de) | 1983-07-22 | 1983-07-22 | Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus | 
Publications (1)
| Publication Number | Publication Date | 
|---|---|
| DE3326472A1 true DE3326472A1 (de) | 1985-02-14 | 
Family
ID=6204660
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date | 
|---|---|---|---|
| DE19833326472 Withdrawn DE3326472A1 (de) | 1983-07-22 | 1983-07-22 | Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus | 
| DE8484108442T Expired DE3466227D1 (en) | 1983-07-22 | 1984-07-18 | Insulin derivatives, processes for their preparation, their use and pharmaceutical compositions for the treatment of diabetes mellitus | 
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date | 
|---|---|---|---|
| DE8484108442T Expired DE3466227D1 (en) | 1983-07-22 | 1984-07-18 | Insulin derivatives, processes for their preparation, their use and pharmaceutical compositions for the treatment of diabetes mellitus | 
Country Status (20)
| Country | Link | 
|---|---|
| US (1) | US4701440A (pm) | 
| EP (1) | EP0132770B1 (pm) | 
| JP (2) | JPS6042397A (pm) | 
| AR (1) | AR241864A1 (pm) | 
| AT (1) | ATE29729T1 (pm) | 
| AU (1) | AU569097B2 (pm) | 
| CA (1) | CA1246548A (pm) | 
| DE (2) | DE3326472A1 (pm) | 
| DK (2) | DK172211B1 (pm) | 
| ES (2) | ES534487A0 (pm) | 
| FI (1) | FI79854C (pm) | 
| GR (1) | GR81551B (pm) | 
| HU (1) | HUT37805A (pm) | 
| IE (1) | IE57709B1 (pm) | 
| IL (1) | IL72469A (pm) | 
| NO (1) | NO167810C (pm) | 
| NZ (1) | NZ208959A (pm) | 
| PH (1) | PH23014A (pm) | 
| PT (1) | PT78940A (pm) | 
| ZA (1) | ZA845620B (pm) | 
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title | 
|---|---|---|---|---|
| DE3327928A1 (de) * | 1983-08-03 | 1985-02-21 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von insulin-derivaten | 
| DE3333640A1 (de) * | 1983-09-17 | 1985-04-25 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von insulin-derivaten, deren b-kette c-terminal verlaengert ist, neue basisch modifizierte insulin-derivate diese enthaltende mittel und ihre verwendung | 
| DE3501641A1 (de) * | 1985-01-19 | 1986-07-24 | Hoechst Ag, 6230 Frankfurt | Verfahren zur gewinnung von insulin-vorlaeufern aus reaktionsgemischen, die bei der faltung von insulin-vorlaeufern aus den entsprechenden s-sulfonaten anfallen | 
| US4946828A (en) * | 1985-03-12 | 1990-08-07 | Novo Nordisk A/S | Novel insulin peptides | 
| DK113585D0 (da) * | 1985-03-12 | 1985-03-12 | Novo Industri As | Nye peptider | 
| US4764592A (en) * | 1987-04-23 | 1988-08-16 | Eli Lilly And Company | Crystalline human proinsulin and process for its production | 
| DE3717370A1 (de) * | 1987-05-22 | 1988-12-01 | Hoechst Ag | Mischkristalle aus insulin und insulinderivaten, verfahren zur herstellung dieser mischkristalle, diese mischkristalle enthaltende pharmazeutische mittel und ihre verwendung zur behandlung von diabetes mellitus | 
| US4789660A (en) * | 1987-09-10 | 1988-12-06 | American Home Products Corporation | Insulin administration using methyl and propyl paraben | 
| DE3827533A1 (de) * | 1988-08-13 | 1990-02-15 | Hoechst Ag | Pharmazeutische zubereitung zur behandlung des diabetes mellitus | 
| DE3837825A1 (de) * | 1988-11-08 | 1990-05-10 | Hoechst Ag | Neue insulinderivate, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung | 
| US5716927A (en) * | 1988-12-23 | 1998-02-10 | Novo Nordisk A/S | Insulin analogs having a modified B-chain | 
| HUT56857A (en) * | 1988-12-23 | 1991-10-28 | Novo Nordisk As | Human insulin analogues | 
| DK134189D0 (da) * | 1989-03-20 | 1989-03-20 | Nordisk Gentofte | Insulinforbindelser | 
| DE3936876A1 (de) * | 1989-11-06 | 1991-05-23 | Hoechst Ag | Neue insulinderivate, verfahren zu deren herstellung, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung | 
| AU9172991A (en) | 1990-12-07 | 1992-07-08 | Cnc Development, Inc. | Catalytic chemical reactor | 
| YU66892A (sh) * | 1991-08-20 | 1995-10-24 | Hoechst Ag. | Fosfoinositolglikan - peptid sa delovanjem kao insulin | 
| TW224471B (pm) * | 1991-11-26 | 1994-06-01 | Lilly Co Eli | |
| DK0545198T3 (da) * | 1991-11-29 | 2000-03-20 | Hoechst Ag | Peptider med insulinagtig virkning | 
| US5504188A (en) * | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals | 
| DK0821006T3 (da) | 1996-07-26 | 2004-08-16 | Aventis Pharma Gmbh | Insulinderivater med öget zinkbinding | 
| DE19649350A1 (de) * | 1996-11-28 | 1998-06-04 | Hoechst Ag | Inositolglykane mit insulinartiger Wirkung | 
| US6444641B1 (en) | 1997-10-24 | 2002-09-03 | Eli Lilly Company | Fatty acid-acylated insulin analogs | 
| DE19825447A1 (de) | 1998-06-06 | 1999-12-09 | Hoechst Marion Roussel De Gmbh | Neue Insulinanaloga mit erhöhter Zinkbildung | 
| WO2000075365A2 (en) | 1999-06-08 | 2000-12-14 | University Of Iowa Research Foundation | Compounds and methods to enhance raav transduction | 
| WO2002067969A2 (en) | 2001-02-21 | 2002-09-06 | Medtronic Minimed, Inc. | Stabilized insulin formulations | 
| CN1177920C (zh) * | 2001-02-21 | 2004-12-01 | 株式会社正和·专门 | 附着于钛材上的水垢的去除剂 | 
| DE10114178A1 (de) | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität | 
| DE10227232A1 (de) * | 2002-06-18 | 2004-01-15 | Aventis Pharma Deutschland Gmbh | Saure Insulinzubereitungen mit verbesserter Stabilität | 
| CA2520016A1 (en) | 2003-03-31 | 2004-10-21 | University Of Iowa Research Foundation | Pharmico-gene therapy of epithelial sodium channel associated disorders | 
| EP2316844A3 (en) * | 2003-05-21 | 2011-07-20 | Biotech Tools S.A. | Peptide complex | 
| US7833513B2 (en) | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease | 
| CR20170369A (es) | 2008-10-17 | 2017-11-01 | Sanofi Aventis Deutschland | COMBINACIÓN DE UNA INSULINA Y UN AGONISTA DE GLP-1 (Divisional 2011-0188) | 
| WO2011058082A1 (de) | 2009-11-13 | 2011-05-19 | Sanofi-Aventis Deutschland Gmbh | Pharmazeutische zusammensetzung umfassend einen glp-1-agonisten und methionin | 
| PL2498802T3 (pl) | 2009-11-13 | 2015-06-30 | Sanofi Aventis Deutschland | Kompozycja farmaceutyczna zawierająca agonistę GLP-1, insulinę i metioninę | 
| SG187904A1 (en) | 2010-08-30 | 2013-04-30 | Sanofi Aventis Deutschland | Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2 | 
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin | 
| EP2750699B1 (en) | 2011-08-29 | 2015-07-22 | Sanofi-Aventis Deutschland GmbH | Pharmaceutical combination for use in glycemic control in diabetes type 2 patients | 
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease | 
| EP3229828B1 (en) | 2014-12-12 | 2023-04-05 | Sanofi-Aventis Deutschland GmbH | Insulin glargine/lixisenatide fixed ratio formulation | 
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患治療 | 
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患之治療 | 
| WO2017139381A1 (en) | 2016-02-08 | 2017-08-17 | University Of Iowa Research Foundation | Methods to produce chimeric adeno-associated virus/bocavirus parvovirus | 
| MX2018010842A (es) | 2016-03-07 | 2019-07-04 | Univ Iowa Res Found | Expresion mediada por el virus adeno-asociado (aav) usando un promotor y pontenciador sintetico. | 
| US12173305B2 (en) | 2016-05-26 | 2024-12-24 | University Of Iowa Research Foundation | cis and trans requirements for terminal resolution of human bocavirus 1 | 
| WO2018132747A1 (en) | 2017-01-13 | 2018-07-19 | University Of Iowa Research Foundation | Bocaparvovirus small noncoding rna and uses thereof | 
| JP7439062B2 (ja) | 2018-09-19 | 2024-02-27 | ノヴォ・ノルディスク・リサーチ・センター・オックスフォード・リミテッド | グルコース感受性インスリンおよびその使用 | 
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|---|---|---|---|---|
| DE2256215C3 (de) * | 1972-11-16 | 1981-01-08 | Hoechst Ag, 6000 Frankfurt | Insulin-Zubereitung mit einem Gehalt an kristallinem Insulin und amorphem Desphenylalanin8' -insulin | 
| DE2460753A1 (de) * | 1974-12-21 | 1976-06-24 | Hoechst Ag | Verfahren zur herstellung von humaninsulin | 
| DE3064479D1 (en) * | 1979-04-13 | 1983-09-08 | Shionogi & Co | Process for preparing a b30-threonine insulin | 
| DK319780A (da) * | 1980-07-24 | 1982-01-25 | Forenede Bryggerier As | Fremgangsmaade til enzymatisk udskiftning af b-30 aminosyren i insuliner | 
| DE3209184A1 (de) * | 1982-03-13 | 1983-09-15 | Hoechst Ag, 6230 Frankfurt | Verfahren zur umwandlung von praeproinsulinanaloga zu insulinen | 
| NL8201650A (nl) * | 1982-04-21 | 1983-11-16 | Akzo Nv | Semisynthetische bereiding van humane insuline. | 
| DE3327928A1 (de) * | 1983-08-03 | 1985-02-21 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von insulin-derivaten | 
| DE3333640A1 (de) * | 1983-09-17 | 1985-04-25 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von insulin-derivaten, deren b-kette c-terminal verlaengert ist, neue basisch modifizierte insulin-derivate diese enthaltende mittel und ihre verwendung | 
| DE3334407A1 (de) * | 1983-09-23 | 1985-04-04 | Hoechst Ag, 6230 Frankfurt | In position b 30 modifizierte insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus | 
| JPH118546A (ja) * | 1997-04-24 | 1999-01-12 | Hitachi Ltd | Cmos回路 | 
- 
        1983
        
- 1983-07-22 DE DE19833326472 patent/DE3326472A1/de not_active Withdrawn
 
 - 
        1984
        
- 1984-07-16 HU HU842766A patent/HUT37805A/hu unknown
 - 1984-07-17 AR AR84297267A patent/AR241864A1/es active
 - 1984-07-18 DE DE8484108442T patent/DE3466227D1/de not_active Expired
 - 1984-07-18 AT AT84108442T patent/ATE29729T1/de not_active IP Right Cessation
 - 1984-07-18 EP EP84108442A patent/EP0132770B1/de not_active Expired
 - 1984-07-18 GR GR75343A patent/GR81551B/el unknown
 - 1984-07-19 PT PT78940A patent/PT78940A/pt not_active IP Right Cessation
 - 1984-07-19 FI FI842914A patent/FI79854C/fi not_active IP Right Cessation
 - 1984-07-20 IL IL72469A patent/IL72469A/xx not_active IP Right Cessation
 - 1984-07-20 PH PH31009A patent/PH23014A/en unknown
 - 1984-07-20 ZA ZA845620A patent/ZA845620B/xx unknown
 - 1984-07-20 ES ES534487A patent/ES534487A0/es active Granted
 - 1984-07-20 IE IE1889/84A patent/IE57709B1/en not_active IP Right Cessation
 - 1984-07-20 NO NO842977A patent/NO167810C/no not_active IP Right Cessation
 - 1984-07-20 JP JP59149784A patent/JPS6042397A/ja active Granted
 - 1984-07-20 AU AU30922/84A patent/AU569097B2/en not_active Ceased
 - 1984-07-20 CA CA000459386A patent/CA1246548A/en not_active Expired
 - 1984-07-20 DK DK358284A patent/DK172211B1/da not_active IP Right Cessation
 - 1984-07-20 NZ NZ208959A patent/NZ208959A/xx unknown
 - 1984-09-06 ES ES535706A patent/ES8505646A1/es not_active Expired
 
 - 
        1986
        
- 1986-06-06 US US06/873,456 patent/US4701440A/en not_active Expired - Lifetime
 
 - 
        1989
        
- 1989-02-22 JP JP1040427A patent/JPH01294634A/ja active Granted
 
 - 
        1990
        
- 1990-01-04 DK DK001790A patent/DK172209B1/da not_active IP Right Cessation
 
 
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